Transient receptor potential channels as novel effectors of brain-derived neurotrophic factor signaling: Potential implications for Rett syndrome

Abstract

In addition to their prominent role as survival signals for neurons in the developing nervous system, neurotrophins have established their significance in the adult brain as well, where their modulation of synaptic transmission and plasticity may participate in associative learning and memory. These crucial activities are primarily the result of neurotrophin regulation of intracellular Ca 2+ homeostasis and, ultimately, changes in gene expression. Outlined in the following review is a synopsis of neurotrophin signaling with a particular focus upon BDNF and its role in hippocampal synaptic plasticity and neuronal Ca 2+ homeostasis. Neurotrophin signaling through Trk and p75 NTR receptors are also discussed, reviewing recent results that indicate signaling through these two receptor modalities leads to opposing cellular outcomes. We also provide an intriguing look into the TRPC family of ion channels as distinctive targets of BDNF signaling; these channels are critical for capacitative Ca 2+ entry, which, in due course, mediates changes in neuronal structure including dendritic spine density. Finally, we expand these topics into an exploration of mental retardation, in particular Rett Syndrome, where dendritic spine abnormalities may underlie cognitive impairments. We propose that understanding the role of neurotrophins in synapse formation, plasticity and maintenance will make fundamental contributions to the development of therapeutic strategies to improve cognitive functions in developmental disorders associated with mental retardation.

Nanoparticle-mediated signaling endosome localization regulates growth cone motility and neurite growth

“…These data also suggest that altering signaling endosome localization may provide a unique method to study retrograde flow, myosin activity, and protrusive activity in the peripheral domain of the growth cone. Moreover, altered signaling endosome localization may provide a unique method for evaluating current hypotheses on the role that TrkB signaling endosome localization plays in other known signaling endosome-dependent processes such as cell migration (18), synaptic plasticity (45,46), calcium signaling (47,48), and learning and memory (49).…”

The actions of BDNF on dendritic spine density and morphology in organotypic slice cultures depend on the presence of serum in culture media

“…Along with several other physiological consequences of BDNF signaling in the hippocampus, i.e. modulation of presynaptic function (Tyler et al, 2002b), BDNF-induced dendritic remodeling likely contributes to its role in the establishment and activity-dependent refinement of neuronal networks necessary and fundamental for synaptic plasticity and hippocampal-dependent learning and memory (Amaral et al, 2007;Amaral and Pozzo-Miller, 2005;Bramham and Messaoudi, 2005;Chapleau and Pozzo-Miller, 2007;Tyler et al, 2002a). Hippocampal slice cultures were transfected with eYFP using a gene-gun and processed for laser-scanning confocal microscopy.…”

“…In addition to these classical functions, BDNF in particular has been shown to be one of the most potent modulators of synaptic transmission and plasticity, as well as neuronal and synaptic morphology (Amaral et al, 2007;Black, 1999;Poo, 2001;Tyler et al, 2002a;Vicario-Abejon et al, 2002). Each neurotrophin exerts its actions through binding and activation of specific, membrane-bound tropomyosin-related kinase (Trk) receptors, or a single pan-neurotrophin receptor, the so-called p75NTR (Barbacid, 1993).…”

Lack of Kinase Regulation of Canonical Transient Receptor Potential 3 (TRPC3) Channel-dependent Currents in Cerebellar Purkinje Cells

“…9 and 10) and underlie the slow excitatory postsynaptic potentials (EPSPs) observed in a number of neurons after release of brainderived neurotrophic factor or glutamate (10 -13). Brain-derived neurotrophic factor-mediated activation of TRPC induced changes in dendritic spine density, which suggests that they can influence synaptic plasticity and may hence be crucially involved in processes such as memory formation (10,14). However, there is very little information about a distinct physiological role of an identified brain TRPC channel in the behaving animal.…”